title: Effect of co-transporter blockers on non-synaptic epileptiform activity-computational simulation.
abstract: The important role of cation-chloride co-transporters in epilepsy is being supported by an increasing number of investigations. However, enormous complexity is involved since the action of these co-transporters has effects on the ionic homeostasis influencing directly the neuronal excitability and the tissue propensity to sustain seizure. To unravel the complex mechanisms involving the co-transporters action during seizure, this paper shows simulations of non-synaptic epileptiform activity and the effect of the blockage of the two different types of cation-chloride co-transporters present in the brain: Na, K and 2Cl co-transporter (NKCC) and K and Cl co-transporter (KCC). The simulations were performed with an electrochemical model representing the non-synaptic structure of the granule cell layer of the dentate gyrus (DG) of the rat hippocampus. The simulations suggest: (i) the potassium clearance is based on the systemic interplay between the Na/K pump and the NKCC co-transporters; (ii) the simultaneous blockage of the NKCC of the neurons and KCC of glial cells acts efficiently suppressing the epileptiform activities; and (iii) the simulations show that depending on the combined blockage of the co-transporters, the epileptiform activities may be suppressed or enhanced.
authors.affiliation: Departamento de Engenharia de Biossistemas, Universidade Federal de São João del-Rei, São João del-Rei-MG, 39301-160-Brazil.
authors.forename: Mariana Rodrigues
authors.initials: MR
authors.lastname: Lopes
authors.forename: Luiz Eduardo Canton
authors.initials: LE
authors.lastname: Santos
authors.forename: Antônio Márcio
authors.initials: AM
authors.lastname: Rodrigues
authors.forename: Mario Antônio
authors.initials: MA
authors.lastname: Duarte
authors.forename: Antonio Fernando Catelli
authors.initials: AF
authors.lastname: Infantosi
authors.forename: Fulvio Alexandre
authors.initials: FA
authors.lastname: Scorza
authors.forename: Ricardo Mario
authors.initials: RM
authors.lastname: Arida
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Madureira
authors.forename: Gilcélio Amaral
authors.initials: GA
authors.lastname: da Silveira
authors.forename: Ivans Carlos
authors.initials: IC
authors.lastname: dos Santos
authors.forename: Esper Abrão
authors.initials: EA
authors.lastname: Cavalheiro
authors.forename: Antônio-Carlos Guimarães
authors.initials: AC
authors.lastname: de Almeida
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects*; D027981:Symporters / Q000037:antagonists & inhibitors*; D000096922:K Cl- Cotransporters
chemical_list: D028021:Sodium-Potassium-Chloride Symporters; D027981:Symporters; D000096922:K Cl- Cotransporters